title: Chromosomal mosaicism in mouse two-cell embryos after paternal exposure to acrylamide.
abstract: Chromosomal mosaicism in human preimplantation embryos is a common cause of spontaneous abortions, however, our knowledge of its etiology is limited. We used multicolor fluorescence in situ hybridization painting to investigate whether paternally transmitted chromosomal aberrations result in mosaicism in mouse two-cell embryos. Paternal exposure to acrylamide, an important industrial chemical also found in tobacco smoke and generated during the cooking process of starchy foods, produced significant increases in chromosomally defective two-cell embryos, however, the effects were transient primarily affecting the postmeiotic stages of spermatogenesis. Comparisons with our previous study of zygotes demonstrated similar frequencies of chromosomally abnormal zygotes and two-cell embryos suggesting that there was no apparent selection against numerical or structural chromosomal aberrations. However, the majority of affected two-cell embryos were mosaics showing different chromosomal abnormalities in the two blastomeric metaphases. Analyses of chromosomal aberrations in zygotes and two-cell embryos showed a tendency for loss of acentric fragments during the first mitotic division of embryogenesis, whereas both dicentrics and translocations apparently underwent proper segregation. These results suggest that embryonic development can proceed up to the end of the second cell cycle of development in the presence of abnormal paternal chromosomes and that even dicentrics can persist through cell division. The high incidence of chromosomally mosaic two-cell embryos suggests that the first mitotic division of embryogenesis is prone to missegregation errors and that paternally transmitted chromosomal abnormalities increase the risk of missegregation leading to embryonic mosaicism.
authors.affiliation: Biosciences Directorate, Lawrence Livermore National Laboratory, Livermore, California 94550, USA.
authors.forename: Francesco
authors.initials: F
authors.lastname: Marchetti
authors.forename: Jack
authors.initials: J
authors.lastname: Bishop
authors.forename: Xiu
authors.initials: X
authors.lastname: Lowe
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Wyrobek
mesh_terms: D020106:Acrylamide / Q000633:toxicity*; D000704:Analysis of Variance; D000818:Animals; D019457:Chromosome Breakage / Q000187:drug effects; D020223:Chromosome Painting; D053938:DNA Fragmentation / Q000187:drug effects; D004622:Embryo, Mammalian / Q000187:drug effects* / Q000648:ultrastructure; D005260:Female; D005306:Fertilization / Q000187:drug effects; D015321:Gene Rearrangement / Q000187:drug effects; D007211:Indoles; D007274:Injections, Intraperitoneal; D008297:Male; D008677:Metaphase / Q000187:drug effects; D051379:Mice; D009030:Mosaicism / Q000139:chemically induced*; D018812:Paternal Exposure / Q000009:adverse effects*; D011247:Pregnancy; D013091:Spermatogenesis / Q000187:drug effects; D014178:Translocation, Genetic / Q000187:drug effects; D015053:Zygote / Q000187:drug effects* / Q000648:ultrastructure
chemical_list: D007211:Indoles; D020106:Acrylamide; C007293:DAPI